Non-steroidal Anti-inflammatory Ibuprofen Research Articles

Impact of hemoglobin A1c level on the association between non-steroidal anti-inflammatory drug use and cardiovascular events in patients with type 2 diabetes: A population-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes. We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol). For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol. In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use.

Development of an electrochemical cyclooxygenase biosensor to evaluate target–drug viability and interactions

In this research, we developed a biosensor to analyze the anti-inflammatory properties of non-steroidal anti-inflammatory drugs (NSAIDs) and potential candidate molecules. The chemical interaction between commercial NSAIDs and their target, the cyclooxygenase-2 enzyme (COX), was studied using electrochemical techniques and electronic paramagnetic resonance (EPR). The modified electrode, COX@GCE biosensor, presented two main reduction processes. We observed that the first one involves one electron and one proton related to tyrosyl radical reduction to tyrosine, and the second comprises a one-electron reduction from the Fe (IV) to Fe (III) species present in the enzyme’s active site, which in the presence of hydrogen peroxide results in a catalytical process. Based on these results, an electrochemical mechanism of the COX enzyme is proposed. Additionally, the quantitative inhibitory interaction mechanisms of six commercial NSAIDs were studied using this biosensor. The NSAIDs acetylsalicylic acid, dipyrone, and ibuprofen presented the higher COX inhibitory percentual, being, therefore, the most effective NSAIDs among the studied group. Salicylic acid also presented a significant inhibition capability in both electrochemical and EPR studies. The effect of some NSAIDs, e.g., dipyrone and acetaminophen, can be explained by the redox inhibition hypothesis and can be related to the direct interaction and inactivation of the iron present in the enzyme’s active site. Ibuprofen and naproxen presented irreversible COX inhibition. Despite that, the EPR shows that these drugs have relatively weak interactions with the COX active site, suggesting they should interact with the external structures resulting in the inhibition of its activity. Finally, the developed enzymatic sensor presented a high potential to study the anti-inflammatory properties of well-known drugs and can be a useful tool in the development of new NSAIDs, in a more efficient way, therefore presenting high applicability in drug development, pharmaceutical, and biomedical applications in both academia and industry.

In vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of heteroleptic silver(I), nickel(II) and copper(II) complexes of 4-methyl-3-thiosemicarbazones and ibuprofen

ObjectivesThe present research focuses on the in vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of twelve heteroleptic metal complexes of the general formulae [Ag(L1−4)(ibu)] (1–4) and [M(L1−4)(ibu)2] (5–12), where L1−4 = 2-(1-(4-substitutedphenyl)ethylidene)-N-methylhydrazinecarbothioamide, ibu = non-steroidal anti-inflammatory drug (ibuprofen), and M = Cu(II) and Ni(II). MethodsVarious spectroscopic techniques were used to authenticate the structure of the synthesized complexes. UV-Vis and cyclic voltammetry techniques were used to analyse the stability and the reducing ability of the complexes. In vitro anti-proliferative studies by MTT assay, apoptotic behaviour and cellular uptake studies were investigated followed by the in silico interaction with ribonucleotide reductase (RNR) enzyme. ResultsThe spectral studies predicted distorted tetrahedral geometry around silver(I) ion and distorted octahedral geometry around nickel(II) and copper(II) ions. The reducing ability of the copper(II) complexes was analysed using ascorbic acid by UV-Vis and cyclic voltammetry techniques, which authenticate the reducing ability of the complexes and the possible interactions within the cells. The in vitro anti-proliferative activity of the synthesized complexes against three cancerous (estrogen positive (MCF-7), estrogen negative (MDA-MB-231) and pancreatic (PANC-1)) and one normal (MCF-10a) cell lines by MTT assay showed enhanced activity for copper(II) complexes 11 and 12 containing the hydrophobic substituents. The apoptotic and cellular uptake studies showed that the complex 12 is readily taken up by PANC-1 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. The in silico studies indicated hydrogen bonding, hydrophobic and π-pair (π–π, π–σ and π–cation) interactions between the complexes and the ribonucleotide reductase (RNR) enzyme. The in silico pharmacokinetics studies of the complexes predicted the drug-likeness characteristics of the complexes. ConclusionThe synthesized complexes are found to be less toxic to normal cells and inhibit the growth of cancerous cells by inducing mitochondrial-mediated and caspase dependent apoptotic pathway in PANC-1 cells.

Spatial variations and ecological risks assessment of pharmaceuticals and personal care products (PPCPs) in typical lakes of Wuhan, China

Lakes are terminal sink of PPCPs, since PPCPs were transported to aquatic system from wastewater treatment plant effluent. Meanwhile, the ecological risks caused by PPCPs to the lakes have aroused wide concern. This study investigated the presence and distribution of PPCPs in 19 typical lakes in Wuhan city; the short term and long-term ecological risk were assessed. The concentration of ten typical PPCPs and the correlation between PPCPs and water quality parameters were analyzed. Ten PPCPs were widely detected, showing that these PPCPs were abundant in the research region. The total PPCPs concentrations varied from 0.44 to 2.1 * 102 ng/L in water sample and ≤ 5.3 ng/g in sediments. According to the results, two nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) were predominated compared to other PPCPs tested in the lakes of Wuhan city. The Pearson correlation analysis revealed a substantial positive correlation (p < 0.01) between NH4+-N and ibuprofen concentration, indicating that ibuprofen could be produced from the same sources of NH4+-N. Some PPCPs has shown positive correlation (p < 0.01) with suspended particles in concentrations. A negative correlation in water-sediment distribution for PPCPs was also observed. The potential ecological risks of PPCPs to the lakes were further evaluated. Results implied that ofloxacin posed the highest potential short-term risk of all the ten PPCPs. Sulfadiazine, sulfamethoxazole and roxithromycin posed a potential long-term risk in Niushan lake. This study investigated PPCPs distribution on a large spatial scale in Wuhan lakes in the post-epidemic era and revealed the importance of ofloxacin control in Wuhan. The findings of this work suggests that the long-term management for lake ecosystems is crucial.

Neonicotinoids and pharmaceuticals in hair of the Red fox (Vulpes vulpes) from the Cavallino-Treporti peninsula, Italy

Neonicotinoids (NEOs) and active pharmaceuticals ingredients (API) are contaminants widely diffused worldwide, causing increasing concern for potential adverse effects on wildlife. However, research on these contaminants have focused on target and non-target invertebrates, while information on potential effects in terrestrial mammals is lacking. We performed preliminary non-invasive monitoring of NEOs and API in a suburban and agricultural area using hair of the Red fox. The Red fox is a widely diffused mesopredator in Europe, and its plasticity in feeding habits makes it an excellent indicator for assessing exposure to environmental contamination. We observed the presence of NEOs in many Red fox hair samples (n = 11), including imidacloprid (IMI), acetamiprid (ACE), and clothianidin (CLO). The highest quantified concentrations were 6.4 ng g−1 dry weight (dw), 6.7 ng g−1 dw, and 0.9 ng g−1 dw for IMI, ACE, and CLO, respectively. The targeted APIs included non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants. APIs were less frequently detected than NEOs, and the compounds with the highest prevalence were the NSAID ketoprofen (36%), the antidepressant sertraline (36%), and its active metabolite norsertraline (27%). The presence of human pharmaceuticals such as the NSAID ibuprofen and the antidepressants sertraline, fluoxetine, and their active metabolites norsertraline and norfluoxetine suggest environmental contamination due to untreated and partially treated wastewater discharged in surface waters and soils of the study area. The detection and quantification of ketoprofen and flunixin also suggest the possible use of contaminated manure on farmland. Findings indicate that hair may be used for monitoring environmental exposure to NEOs and provide evidence that hair is a good marker of exposure for antidepressants and certain NSAIDs, including ibuprofen, ketoprofen, and flunixin.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Epipericardial fat necrosis: a case report of an underdiagnosed disease.

Response of hepatic biochemical parameters and neurotoxicity to carbamazepine and ibuprofen in Oreochromis mossambicus.

Globally, the prevalence and pollution of pharmaceutical drugs in aquatic environments have been steadily increasing. This study sought to evaluate the effects of 14days of exposure to environmental-relevant doses (ibuprofen 0.5, 5, and 50µg/L, and carbamazepine 0.005, 1, and 10µg/L) of the nonsteroidal anti-inflammatory drugs ibuprofen and carbamazepine in the freshwater fish Oreochromis mossambicus. The results showed a significant (P < 0.05) decrease in O. mossambicus superoxide dismutase, catalase, biotransformation enzymes, glutathione-s-transferase, glutathione peroxidase, oxidative stress lipid peroxidation, protein carbonyl activity, cellular damage metallothionine, reduced glutathione, immunological activities, and respiratory burst activity. Consequently, the acquired data revealed that O. mossambicus treated with ibuprofen and carbamazepine shows more significant alterations in metabolic depression, biochemical parameters, and oxidative stress. In addition, increased neurotoxic effects were observed in ibuprofen and carbamazepine treated O. mossambicus.

Twin Screw Melt Granulation: Alternative Approach for Improving Solubility and Permeability of a Non-steroidal Anti-inflammatory Drug Ibuprofen.

The current research is focused on investigating the suitability of the twin screw melt granulation (TSMG) approach for improving the solubility of a non-steroidal anti-inflammatory (NSAIDs) drug (ibuprofen), by developing granules using lipid surfactants. The solubility of the drug within the solid lipid excipients (Gelucire® 48/16 and Gelucire® 50/13) was determined by differential scanning calorimetry (DSC). The formulations were developed for drug and lipid ratios of 1:1.5, 1:3, and 1:4.5 using Neusilin® US2 as a solid adsorbent carrier. The solid-state properties of the drug investigated using differential scanning calorimetry (DSC) have revealed the conversion of the drug to an amorphous form for 1:3 and 1:4.5 ratios of formulations confirmed by powder x-ray diffraction analysis (PXRD). Drug-excipient compatibility and formation of no interactions were characterized using Fourier transform infrared spectroscopy (FTIR). The granules with a 1:3 and 1:4.5 ratios of drug and lipid have improved drug dissolution and permeation, attributing to the formation of micellar emulsions. The stability of formulation with a 1:3 ratio of drug and lipid surfactant was preserved when stored in accelerated conditions. However, the formulation with a 1:4.5 ratio of drug and lipid failed to retain the amorphous state evidenced by the recrystallization of the drug. This shows the suitability of TSMG as a single-step continuous manufacturing process for developing melt granules to improve the solubility of poorly water-soluble drug substances.

Adsorption of the non-steroidal anti-inflammatory drug (ibuprofen) onto biochar and magnetic biochar prepared from chrysanthemum waste of the beverage industry.

Biochar and magnetic biochar prepared from chrysanthemum waste of the beverage industry are effective adsorbents for the removal of the non-steroidal anti-inflammatory drug, ibuprofen (IBP), from aqueous systems. The development of magnetic biochar using iron chloride, overcame poor separation characteristics from the liquid phase of the powdered biochar after adsorption. Characterisation of biochars was achieved through Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), N2 adsorption/desorption porosimetry, scanning electron microscopy (SEM), electron dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), moisture and ash content, bulk density, pH and zero-point charge (pHpzc). The specific surface area of non-magnetic and magnetic biochars was 220 and 194 m2 g-1, respectively. Adsorption of ibuprofen was optimised with respect to contact time (5-180 min), solution pH (2-12) and initial drug concentration (5-100 mg L-1), with equilibrium being reached in 1 hour, and the maximum ibuprofen removal occurred at pH 2 and 4 for biochar and magnetic biochars, respectively. Investigation of the adsorption kinetics was achieved through application of the pseudo-first order, pseudo-second order, Elovich and intra-particle diffusion models. Adsorption equilibrium was evaluated using Langmuir, Freundlich and Langmuir-Freundlich isotherm models. The adsorption kinetics and isotherms for both biochars are well described by pseudo-second order kinetic and Langmuir-Freundlich isotherm models, respectively, with the maximum adsorption capacity of biochar and magnetic biochar being 167 and 140 mg g-1, respectively. Chrysanthemum derived non-magnetic and magnetic biochars exhibited significant potential as sustainable adsorbents toward the removal of emerging pharmaceutical pollutants such as ibuprofen from aqueous solution.

Диференційна діагностика больового синдрому в щелепно-лицевій ділянці. Аналіз клінічного випадку

The purpose of the study was to demonstrate the main stages of a complex examination and differential diagnosis of atypical facial pain on the example of a case from clinical practice. In modern conditions, the diagnosis and effective treatment of pain in the maxillofacial area is based on a multidisciplinary approach. Often, the causes of pain in the face, jaws and tongue are different. The variety of causes, complex and multi-component diagnostic protocols (and as a result, a high risk of diagnostic mistakes) – all that requires deep knowledge of the anatomy, physiology and pathophysiology of the maxillofacial area, without which it is impossible to understand the diagnosis of the above-mentioned diseases. Based on the subjective characteristics of the pain syndrome and neurological symptoms, it is not always possible to reliably establish the etiology of facial pain. It is quite risky to draw final diagnostic conclusions even with relatively high efficiency of prescribed medicine therapy, since the syndromological approach to the treatment of such patients widely used in practice is palliative in nature and does not contain requirements for a clear assessment of the etiological factor. In the case of persistent facial pain, it is important to perform special studies to verify and evaluate the structural changes involved in the process of changing anatomical formations. The presence of objective symptoms is an important criterion in the topical diagnosis of facial prosopalgia. A clinical case of prosopalgia in a 35-year-old female patient with symptoms of trigeminal neuralgia is presented. The patient marked the positive effects from the use of non-steroidal anti-inflammatory drugs (nimesulide and ibuprofen) and antiseizure medications (carbamazepine). A thorough examination of the patient's dental status made it possible to verify the diagnosis – follicular cyst of the left upper jaw from the retained and dislocated 28th tooth, orofacial pain associated with diseases of dento-alveolar and accompanying structures. The surgical treatment made it possible to successfully cure the patient. Differential diagnosis of pain in the maxillofacial area is a difficult task for both dentists and neurologists. Usually, such patients do not apply immediately after the problem arises but after some time, so additional signs of sensory, motor and trophic disorders may be detected in their status. There are often cases when the same etiological factor may cause different clinical symptoms, on the other side, a similar clinical complex is able to develop under the influence of different causes. Keywords: orofacial pain, dento-alveolar disorders, dentistry, differential diagnosis, follicular cyst.

Short-term effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on Danio rerio embryos

Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) without a medical prescription and their frequent prevalence in aquatic habitats, there are major health and environmental issues. NSAIDs have been found in surface water and wastewater in concentrations ranging from ng/L to μg/L all over the world. The purpose of this study was to determine the relationship between NSAIDs (diclofenac, ketoprofen, paracetamol and ibuprofen) exposure and associated adverse effects in the assessment of indirect human health risks posed by Danio rerio (zebrafish) and Environmental Risk Assessment (ERA) of these NSAIDs in aquatic environments. Therefore, the objectives of this study were to (i) reveal abnormality endpoints of early developmental stages, after exposure of zebrafish and (ii) perform an ecological risk assessment of aquatic organisms upon exposure to NSAIDs detected in surface waters based on the risk quotients (RQs) method. According to the toxicity data collected, all of the malformations appeared after diclofenac exposure at all concentrations. The most notable malformations were the lack of pigmentation and an increase in yolk sac volume, with EC50 values of 0.6 and 1.03 mg/L, respectively. The results obtained for the ERA revealed RQs higher than 1 for all the four NSAIDs chosen, posing ecotoxicological pressure in aquatic environments. Overall, our findings provide a critical contribution to the formulation of high-priority actions, sustainable strategies and strict regulations that minimize the negative effects of NSAIDs on the aquatic ecosystem.•To determine the LC50, lethal conditions such as coagulation, absence of heartbeat and blood flow, absence of tail separation and development of somites were taken into account.•The EC50 was calculated using sublethal parameters such as blood coagulation, pericardial edema, yolk sac edema or hypertrophy.•The 4 compounds present a high risk individually and in mixture with a RQ >> 1.

A tunable family of CAAC-ruthenium olefin metathesis catalysts modularly derived from a large-scale produced ibuprofen intermediate.

A series of tunable CAAC-based ruthenium benzylidene complexes with increased lipophilicity derived from a ketone being a large-scale produced key substrate for a popular nonsteroidal anti-inflammatory drug-ibuprofen was obtained and tested in various olefin metathesis transformations. As a group, these catalysts exhibited higher activity than their known analogues containing a smaller and less lipophilic phenyl substituent on the α-carbon atom, but in individual reactions, the size of the N-aryl moiety was revealed as a decisive factor. For example, in the cross-metathesis of methyl oleate with ethylene (ethenolysis)-a reaction with growing industrial potential-the best results were obtained when the N-aryl contained an isopropyl or tert-butyl substituent in the ortho position. At the same time, in the RCM, CM, and self-CM transformations involving larger olefinic substrates, the catalysts with smaller aryl-bearing CAAC ligands, where methyl and ethyl groups occupy ortho, ortho' positions performed better. This offers a great deal of tunability and allows for selection of the best catalyst for a given reaction while keeping the general structure (and manufacturing method) of the ibuprofen-intermediate derived CAAC ligand the same.

Nonsteroidal anti-inflammatory drugs as a targeted therapy for bone marrow failure in Ghosal hematodiaphyseal dysplasia

AbstractAdvances in genomic diagnostics hold promise for improved care of rare hematologic diseases. Here, we describe a novel targeted therapeutic approach for Ghosal hematodiaphyseal dysplasia, an autosomal recessive disease characterized by severe normocytic anemia and bone abnormalities due to loss-of-function mutations in thromboxane A synthase 1 (TBXAS1). TBXAS1 metabolizes prostaglandin H2 (PGH2), a cyclooxygenase (COX) product of arachidonic acid, into thromboxane A2. Loss-of-function mutations in TBXAS result in an increase in PGH2 availability for other PG synthases. The current treatment for Ghosal hematodiaphyseal dysplasia syndrome consists of corticosteroids. We hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and COX-2, could ameliorate the effects of TBXAS1 loss and improve hematologic function by reducing prostaglandin formation. We treated 2 patients with Ghosal hematodiaphyseal dysplasia syndrome, an adult and a child, with standard doses of NSAIDs (aspirin or ibuprofen). Both patients had rapid improvements concerning hematologic parameters and inflammatory markers without adverse events. Mass spectrometry analysis demonstrated that urinary PG metabolites were increased along with proinflammatory lipoxygenase (LOX) products 5-hydroxyeicosatetraenoic acid and leukotriene E4. Our data show that NSAIDs at standard doses surprisingly reduced both COX and LOX products, leading to the resolution of cytopenia, and should be considered for first-line treatment for Ghosal hematodiaphyseal dysplasia syndrome.

Functionalization of graphene nanostructures with inorganic nanoparticles and their use for the removal of pharmaceutical pollutants in water

Emerging pollutants such as pharmaceuticals are of special concern because despite their low environmental concentration, their biological activity can be intense, and they should be prevented to reach uncontrolledly to the environment. A graphene-based hybrid material decorated with Fe3O4 and TiO2 nanoparticles (NPs) has been prepared to effectively remove emerging pollutants as nonsteroidal anti-inflammatory drugs (NSAIDs) Ibuprofen and Diclofenac present in water at low environmental concentrations by a one-step functionalization process following a novel gentle and scalable surfactant depletion approach. Following this methodology, nanoparticles are progressively deprived of their original surfactant in the presence of graphene, leading to the formation of hybrid nanostructures composed of two different types of nanoparticles well dispersed over the graphene nanosheets. Ibuprofen and Diclofenac adsorption kinetics on the composites was investigated via UV-Vis spectroscopy. The as prepared hybrid material possesses high adsorption capacity, superparamagnetic properties, photocatalytic behavior, and good water dispersibility. Thanks to incorporating TiO2 nanoparticles as in situ catalysts, the adsorption performance of composites is restored after use, which could be a promising recycling pathway for the adsorbents in wastewater treatments.

Biophysical investigation of the interaction between NSAID ibuprofen and cationic biodegradable Cm-E2O2-Cm gemini surfactants

The surfactant-based drug delivery phenomenon has recently received tremendous interest from researchers and pharmaceutical industries. Moreover, a significant shift has been recorded from conventional surfactants to gemini surfactants owing to the advanced chemical and environmental properties of the latter. They are also found to be easily tunable to suit the research and industry requirements. In this work, we have explored the binding interactivity of the non-steroidal anti-inflammatory drug Ibuprofen (IBF) with finely tuned di-ester-based cationic Cm-E2O2-Cm gemini surfactants (where m = alkyl chain length, viz. 12, 14, and 16 and E2O2 is di-ester based spacer) below and above CMC levels. Modification in the surface and interfacial properties of the geminis occurred showing the presence of an interaction between the participants of the studied systems. Fluorescence spectroscopy revealed that the Stern-Volmer constant (Ksv) and binding constant (Kb) follow the same order, which is C12-E2O2-C12 < C16-E2O2-C16 < C14-E2O2-C14 above the CMC but the order changes in the pre-micellar region as C12-E2O2-C12 < C14-E2O2-C14 < C16-E2O2-C16 for Ksv while Kb follows an inverse order. The obtained thermodynamic parameters suggested spontaneous interaction between the examined entities. UV–vis spectroscopic studies (both below and above CMC levels) confirmed the obtained fluorescence results. Additionally, the microenvironment of IBF is changed in the presence of surfactants, suggesting IBF-Cm-E2O2-Cm complexation. FT-IR spectroscopic study also suggests the drug-surfactant complexation. HOMO-LUMO energy gap calculated by the DFT method deduced the feasibility of the interaction. The MD simulation calculations were carried out to find different kind of energies involved in binding process.

On the diffusion of ketoprofen and ibuprofen in water: An experimental and theoretical approach

In view of its importance for the development of dispersion and distribution models in the environment and also for the design of removal methods from wastewaters, the mobility and solute-solvent interaction in aqueous solutions of two non-steroidal anti-inflammatory drugs (ketoprofen and ibuprofen) were studied by measuring mutual diffusion coefficients of each pharmaceutical in water at infinitesimal concentration as a function of temperature, using the Taylor dispersion method. Intra-diffusion coefficients of the same solutes in water at the same temperature range were also calculated by Molecular Dynamics simulations. The analysis of the simulation trajectories allowed the study of the structure of the solvent molecules around the solute and their mutual interaction, which was also addressed by quantum mechanical (DFT) calculations. Ibuprofen presents a higher mutual diffusion coefficient in water than ketoprofen and molecular dynamics simulations are able to predict the experimental values for two solutes. Besides the solute molecular weight and molecular dimensions, the diffusion coefficients of these two pharmaceuticals are influenced by the solute-solvent interactions, which seem to be stronger in the case of ketoprofen. The solvation free energy obtained via DFT calculations confirms that hypothesis.

NSAIDs affect dendritic cell cytokine production.

BackgroundImmunotherapy is now considered as the new pillar in treatment of cancer patients. Dendritic cells (DCs) play an essential role in stimulating anti-tumor immune responses, as they are capable of cross-presenting exogenous tumor antigens in MHCI complexes to activate naïve CD8+ T cells. Analgesics, like non-steroid anti-inflammatory drugs (NSAIDs), are frequently given to cancer patients to help relieve pain, however little is known about their impact on DC function.MethodsHere, we investigated the effect of the NSAIDs diclofenac, ibuprofen and celecoxib on the three key processes of DCs required for proper CD8+ cytotoxic T cell induction: antigen cross-presentation, co-stimulatory marker expression, and cytokine production.ResultsOur results show that TLR-induced pro- and anti-inflammatory cytokine excretion by human monocyte derived and murine bone-marrow derived DCs is diminished after NSAID exposure.ConclusionsThese results indicate that various NSAIDs can affect DC function and warrant further investigation into the impact of NSAIDs on DC priming of T cells and cancer immunotherapy efficacy.

Risk of heart failure following short-term non-steroidal anti-inflammatory drug use in patients with type 2 diabetes mellitus

Abstract Background Fluid retention is a known but underappreciated side-effect of non-steroidal anti-inflammatory drug (NSAID) use. As type 2 diabetes mellitus (T2DM) has been linked to both subclinical cardiomyopathy and a decline in kidney function, short-term NSAID use could lead to subsequently development of heart failure (HF) due to aberrations in fluid balances. Purpose We investigated associations between short-term NSAID use and the risk of HF in a nationwide cohort of patients with T2DM. Methods Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998–2018. Follow-up began 120 days after first-time T2DM diagnosis among patients without prior heart failure or a rheumatological diagnosis indicating long-term NSAID use. To describe use of NSAID among patients with T2DM, we reported proportions of patients claiming at least 1, 2, 3 or 4 prescriptions of NSAID within one year of start of follow-up. We investigated associations between use of NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen) and new-onset HF hospitalizations using a case-crossover design with 28-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). The case-crossover design uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding. Sensitivity analyses using exposure windows of 14 and 42 days were performed as well. Results A total of 334,950 patients with T2DM was included (47.7% female, median age of 61 [interquartile range 50–70]). Celecoxib and naproxen were rarely used; on the contrary, prescriptions of diclofenac and ibuprofen were claimed at least once within one year from the beginning of follow-up by 4.9% and 15.5% of patients, respectively–0.9% and 2.7% claimed at least four prescriptions (Figure 1). The risk of new-onset HF hospitalization was increased following use of diclofenac or ibuprofen with corresponding ORs of 1.3 (95% CI 1.0 to 1.7) and 1.3 (95% CI 1.1 to 1.5) using 28-day exposure windows. An increased risk following use of celecoxib or naproxen was not found (Figure 2). Conclusion NSAIDs diclofenac and ibuprofen were both widely used and associated with an increased risk of new-onset HF hospitalization in patients with T2DM. This suggests a previously unknown and serious, clinically relevant concern of NSAID use in patients with T2DM. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Ib Mogens Kristiansens Almene FondHelsefonden

A miniaturized electrothermal array for rapid analysis of temperature preference behaviors in ecology and ecotoxicology

Due to technical limitations, there have been minimal studies performed on thermal preferences and thermotactic behaviors of aquatic ectotherm species commonly used in ecotoxicity testing. In this work, we demonstrate an innovative, purpose-built and miniaturized electrothermal array for rapid thermal preference behavioral tests. We applied the novel platform to define thermal preferences in multiple invertebrate and vertebrate species. Specifically, Dugesia notogaea (freshwater planarians), Chironomus tepperi (nonbiting midge larvae), Ostracoda (seed shrimp), Artemia franciscana (brine shrimp), Daphnia carinata (water flea), Austrochiltonia subtenuis (freshwater amphipod), Physa acuta (freshwater snail), Potamopyrgus antipodarum (New Zealand mud snail) and larval stage of Danio rerio (zebrafish) were tested. The Australian freshwater water fleas, amphipods, snail Physa acuta as well as zebrafish exhibited the most consistent preference to cool zones and clear avoidance of zones >27 °C out of nine species tested. Our results indicate the larval stage of zebrafish as the most responsive species highly suitable for prospective development of multidimensional behavioral test batteries. We also showcase preliminary data that environmentally relevant concentrations of pharmaceutical pollutants such as non-steroidal anti-inflammatory drug (NSAID) ibuprofen (9800 ng/L) and insecticide imidacloprid (4600 ng/L) but not anti-depressant venlafaxine (2200 ng/L) and (iv) anticonvulsant medications gabapentin (400 ng/L) can perturb thermal preference behavior of larval zebrafish. Collectively our results demonstrate the utility of simple and inexpensive thermoelectric technology in rapid exploration of thermal preference in diverse species of aquatic animals. We postulate that more broadly such technologies can also have added value in ecotoxicity testing of emerging contaminants.

Efficient removal of non-steroidal anti-inflammatory ibuprofen by polypyrrole-functionalized magnetic zeolite from aqueous solution: kinetic, equilibrium, and thermodynamic studies

ABSTRACT This study investigated the adsorption performance of ibuprofen onto magnetic zeolite clinoptilolite modified with polypyrrole (Clino/Fe3O4/Ppy). The synthesized nanocomposite was characterized by scanning electron microscope, Fourier-transform infrared spectroscopy, Energy-dispersive X-ray analysis, Brunauer-Emmett-Teller, and X-ray powder diffraction analysis. The obtained results demonstrated that the high surface area of zeolite could significantly impact the adsorption process. Various parameters were studied to determine the optimum condition, including contact time, pH, adsorbent dosage, initial ibuprofen concentration, temperature, and mixing speed. The optimization of contact time revealed a high performance in the first 5 min of the adsorption process. Furthermore, when the temperature rose, the efficiency increased as well, with the highest efficiency being achieved at 45°C. Some isotherm models and kinetics equations were used to analyze equilibrium data. The kinetic study revealed that the adsorption process followed pseudo-second-order (R2 = 0.9972), and the isotherm investigations showed that Langmuir (R2 = 0.9941) was an appropriate model for explaining the equilibrium of the adsorption process. Based on the obtained thermodynamic factors, it was represented that the adsorption process was endothermic and spontaneous. Based on the research findings, Clino/Fe3O4/PPy nano-adsorbent developed in this study might be a helpful strategy for removing ibuprofen from various water sources.